Pancreatic and Gastroenterology Services, UCL Institute of Child Health and Great Ormond Street Hospital for Children, 30 Guilford Street, London WC1N 1EH, United Kingdom

Abstract

Chronic pancreatitis (CP) is characterised by pancreatic inflammation and fibrosis leading eventually to destruction of pancreatic parenchyma and loss of exocrine and endocrine function. A model of interactions between environmental triggers of pancreatic inflammation and disease susceptibility or modifying genes (including PRSS1, SPINK1 and CFTR) provides a framework within which to understand disease pathogenesis. Early in the disease, when fibrosis is mild and pancreatic damage limited, it is difficult to distinguish CP from recurrent acute pancreatitis (RAP) although it is likely these represent opposite ends of a spectrum of disease with a common aetiology in which CP represents either a later disease stage or disease in individuals predisposed to generate a chronic fibrogenic inflammatory response. Pain is a dominant feature resulting in part from neuroimmune interactions within the pancreas. Diagnosis at an early stage of disease is challenging, though in later stages is dependent upon the demonstration of pancreatic fibrosis and duct ectasia using one or more imaging modalities including transabdominal and endoscopic ultrasound, CT and MRCP or ERCP. Current treatments are largely supportive and reactive. The challenge for pediatricians is to achieve diagnosis at an early stage of the disease and to develop treatments that can alter its natural history.

Keywords: Chronic pancreatitis; Fibrosis; Pancreatic insufficiency; Hereditary pancreatitis; PRSS1; SPINK1; CFTR.

Chronic pancreatitis (CP) is characterised by pancreatic inflammation and fibrosis the endpoint of which is destruction of pancreatic parenchyma with eventual loss of exocrine and endocrine function. The genesis of these endpoints of pancreatic injury may follow years of continual or recurrent injury, implying that pre-clinical or pauci-symptomatic disease is likely to exist earlier in life. Recognition of CP at this pre-clinical or pauci-symptomatic stage is an important challenge for paediatricians when there are opportunities to alter the natural history of CP with the goal of prevention of progression to exocrine and endocrine pancreatic failure and intractable pancreatic pain.

CP is characterised by pancreatic inflammation and fibrosis manifest as irregular glandular sclerosis and (focal or diffuse) destruction of exocrine acinar parenchyma. In later stages, pancreatic duct dilatation, stricture or stone formation are found. CP arises when pancreatic injury is followed by a sustained immune activation in which fibrosis dominates. In normal pancreas, pancreatic stellate cells (PSCs) are quiescent. In response to pancreatic injury or inflammation PSCs may be "activated" into highly proliferative myofibroblast-like cells that express the cytoskeletal protein a-smooth muscle actin (a-SMA) and produce extracellular matrix components including type I collagen. Hence fibrosis follows PSC activation.